Precision Medicine Workshop; Gene Therapy Ian Alexander Professor - - PowerPoint PPT Presentation

Precision Medicine Workshop; Gene Therapy

Ian Alexander

Professor of Paediatrics and Molecular Medicine

Health Informatics Conference

Sydney July 29 - August 1

Just the beginning…….

The Premise of Precision Medicine

Human Genetic Variation

• On average there are 20 million differences in the genomes of any two people
• In excess of 300 million genetic variations are known in the human population
• The average person has approximately 200 faulty genes

Precision Medicine:

A story of three revolutions

• The recombinant DNA revolution
• The DNA sequencing revolution
• The genome engineering revolution

The recombinant DNA revolution

(early 1970s onward) “molecular cut, paste and copy”

The DNA sequencing revolution

(1977 onward)

“We are here to celebrate the completion of the first survey of the entire human genome. Without doubt the most important, most wondrous map ever produced by human kind.” Bill Clinton, June 26th 2000

The inside story of how These bitter rivals mapped

• ur DNA, the historic feat

that changes medicine forever

The genome engineering revolution

(early 2000s onward)

user-designed nucleases

Exciting times!

Medical Implications of Progress in Genomics

Time Progress Knowledge Diagnosis Treatment “gap”

Translational challenges

Gene discovery

(variants of unknown significance)

Functional genomics Health Impact

Prevention and Therapy

Pharmacogenomics Molecular, gene and cellular therapies

Evolving therapeutic strategies

Gene mRNA Protein Cell Tissue/organ

Gene therapy

“the use of genes as medicine” “Simple in concept, complex in practice”

Gene Therapy Clinical Trials

Approved Worldwide 1989-2017

www.wiley.co.uk/genmed/clinical

Gene Therapy

gene addition versus gene repair

• Science (2000), 288: 669-672

A Milestone in Medical History

This transmembrane protein is defective

The g chain of this receptor is common to IL-2,-4,-7,-9,-15 & 21R

Pathophysiology of SCID-X1

• Mutations in IL2RG (gc)

Defective T cell & NK cell differentiation

• Spontaneous reversion events

known to provide cells with a selective advantage in vivo

Chimeric Antigen Receptor T-cell (CAR-T) Immunotherapy for Cancer

Autologous therapy

Also bespoke at the level of the target tumour-associated antigen

The Future – Genome editing

The Future – Genome editing

Take home messages

• Personalized medicine has immense potential that is just beginning to be realised
• Requires deep knowledge of the functional significance of human genetic variation
• Will involve an increasing number of highly bespoke patient-specific interventions
• Will present challenges for bio-therapeutic product manufacture
• Will present challenges to regulators, such as the TGA